The Role of Open‐Shell Organic Radical in Enhancing Anti‐Tumor Photocatalysis Reaction of NIR Light‐Activated Photosensitizer

Open‐shell radical materials, which are characterized by unpaired electrons, have led to revolutionary breakthroughs in material science due to their unique optoelectronic properties. However, the involvement of organic radicals in photodynamic therapy (PDT) has rarely been reported or discussed. This work studies two photosensitizer analogs. 4AM‐OS with extended π‐conjugation exhibits open‐shell radical characters and enhanced type‐I photodynamic activity compared with closed‐shell 2AM‐CS. 4AM‐OS displays the thermally accessible triplet‐state character, resulting in more unpaired electrons delocalized along the π‐conjugated backbone at higher temperatures. Accordingly, the temperature‐dependent photodynamic activity of 4AM‐OS confirms its association with the open‐shell electronic structure. As the unpaired electrons in open‐shell 4AM‐OS are more delocalized and generate additional electronic energy states, photo‐induced charge transfer is promoted to facilitate type‐I photodynamic reactions. This observation addresses the challenge associated with near‐infrared (NIR) photosensitizers, such as 4AM‐OS, which often demonstrate low efficacy in PDT due to the limited energy provided by NIR light despite its superior tissue penetration depth. Overall, clarifying the beneficial role of organic radicals in photodynamic reactions will bring revolutionary breakthroughs to developing high‐performance NIR photosensitizers and promoting the efficacy of PDT for deep‐seated lesions.